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Interactions between T cell receptors (TCRs) and their cognate tumour antigens are central to antitumour immune responses

Background Cell wall architecture plays a key role in stalk strength and forage digestibility. Lignin, cellulose and hemicellulose are the three main components of the plant cell wall and can impact stalk quality by affecting cell wall structure and strength. To explore cell wall development during secondary cell wall lignification in maize stalks, conventional and conditional genetic mappings was used to identify the dynamic quantitative trait locus (QTL) for cell wall components and digestibility traits in five growth stages after silking. Results Acid detergent lignin (ADL), cellulose (CEL), Acid detergent fiber (ADF), neutral detergent fiber (NDF), and in vitro dry matter digestibility (IVDMD) of stalk were evaluated in a maize recombinant inbred line (RIL) population. The cell wall components gradually increased in the 10–40 days after silking (DAS), reached a maximum at 30–40 DAS, and then steadily decreased. IVDMD decreased over the initial 40 DAS and then increased slightly. Seventy-two QTL were identified for five traits and each accounted for 3.48–24.04% of the phenotypic resistance variation. Twenty-six conditional QTL were detected using conditional QTL mapping. 22 out of 24 conditional QTL were found for stages III|II and V|IV. Six QTL hotspots were found localized in bins 1.08, 2.04, 2.07, 7.03, 8.05, and 9.03 in the maize genome. Conclusion The unconditional pleiotropic QTL in bins 1.08 and 8.05 were also associated with stalk strength. Furthermore, several pleiotropic QTL for cell wall and digestibility were found not associated with stalk strength. A simultaneous improvement in forage digestibility and lodging resistance can be achieved by pyramiding multiple effective QTL identified in the present study.

T cells mediate antigen-specific immune responses to disease through the specificity and diversity of their T-cell receptors (TCRs). Although determining the spatial distributions of T cell clonotypes in tissues is essential to understanding T cell maturation and behavior, spatial sequencing methods remain unable to profile the TCR repertoire. We have developed Slide-TCR-seq, a 10-μm-resolution method to sequence whole transcriptomes and TCRs within the spatial context of intact tissues. We first confirmed the ability of Slide-TCR-seq to map the characteristic architecture of T cells and their receptors in mouse spleen. In human reactive lymph node and tonsil, we identified spatially distinct TCR repertoires both between germinal center (GC) and non-GC regions as well as between GCs. We then spatially profiled T cell clonotypes and their infiltration in renal cell carcinoma specimens before and following immune checkpoint blockade, which identified uniquely distributed T cell clonotypes and transcriptional states, highlighting the infiltration and expression heterogeneity both between clonotypes and within a T cell clonotype. Our method is anticipated to facilitate dissection of the immune microenvironment, yielding insights into the complex spatial relationships between T cell clonotypes, neighboring cell types, and gene expression that drive T cell development and response to disease. This work was supported in part by the NIH U19AI082630, the Dana-Farber/Harvard Cancer Center Kidney Cancer SPORE (NCI P50CA101942), and the NCI IMAT grant.

Crassignatha Wunderlich, 1995 is redefined to include species with six eyes in three diads, chelicerae fused only near the base, sculpturing on the carapace, one or two clasping spurs on tibia II, a bilateral scutum of the male abdomen, and globular spermathecae and adjacent copulatory openings in the female. A key and distribution map are provided for 24 Crassignatha species in this paper. Diagnoses and illustrated photographs are provided for 22 species from China, Malaysia, Thailand, and Vietnam. Thirteen species are described and documented as new to science: C. baihua Y. Lin & S. Li, sp. nov. (♂♀), C. bangbie Y. Lin & S. Li, sp. nov. (♀), C. changyan Y. Lin & S. Li, sp. nov. (♀), C. dongnai Y. Lin & S. Li, sp. nov. (♀), C. gucheng Y. Lin & S. Li, sp. nov. (♂♀), C. mengla Y. Lin & S. Li, sp. nov. (♂♀), C. nantou Y. Lin & S. Li, sp. nov. (♂♀), C. nasalis Y. Lin & S. Li, sp. nov. (♂♀), C. rostriformis Y. Lin & S. Li, sp. nov. (♂♀), C. shunani Y. Lin & S. Li, sp. nov. (♂♀), C. si Y. Lin & S. Li, sp. nov. (♂♀), C. thamphra Y. Lin & S. Li, sp. nov. (♀), and C. xichou Y. Lin & S. Li, sp. nov. (♀). Three new combinations are proposed: C. bicorniventris (Lin & Li, 2009), comb. nov., C. quadriventris (Lin & Li, 2009), comb. nov., and C. shiluensis (Lin & Li, 2009), comb. nov. are transferred from Patu Marples, 1951. DNA barcodes and genetic distances of seventeen species are obtained to confirm correct identification. Types of seven known Chinese Crassignatha species are re-examined, and the taxonomic placement of C. longtou Miller, Griswold & Yin, 2009 may be incorrect based on morphological and molecular data.

Five new leptonetid species belonging to Falcileptoneta Komatsu, 1970 and Longileptoneta Seo, 2015 are newly described from South Korea: F. dolsansp. nov. (Jeollanam-do), F. naejangsansp. nov. (Jeollabuk-do), L. buyongsansp. nov. (Chungcheongbuk-do), L. byeonsanbandosp. nov. (Jeollabuk-do) and L. jirisansp. nov. (Gyeongsangnam-do). All new species are found in leaf litter and described from both male and female specimens.

© The Author(s)., CRISPR-Cas9 gene editing has transformed our ability to rapidly interrogate the functional impact of somatic mutations in human cancers. Droplet-based technology enables the analysis of Cas9-introduced gene edits in thousands of single cells. Using this technology, we analyze Ba/F3 cells engineered to express single or multiplexed loss-of-function mutations recurrent in chronic lymphocytic leukemia. Our approach reliably quantifies mutational co-occurrences, zygosity status, and the occurrence of Cas9 edits at single-cell resolution., C.J.W. acknowledges support from the NIH/National Cancer Institute (NIH/NCI) (R01 CA216273, U10 CA180861, P01 CA206978, and P01-CA081534) and is a scholar of the Leukemia and Lymphoma Society. E.t.H. is a Special Fellow of the Leukemia and Lymphoma Society and a Scholar of the American Society of Hematology. S.L. is supported by the NCI Research Specialist Award (R50CA251956-01). L.P. is supported by the National Human Genome Research Institute (NHGRI) Career Development Award (R00HG008399), Genomic Innovator Award (R35HG010717), and CEGS (RM1HG009490). MHS holds a Sara Borrell post-doctoral contract (CD19/00222) from the Instituto de Salud Carlos III (ISCIII) co-founded by Fondo Social Europeo (FSE) “El Fondo Social Europeo invierte en tu futuro”. M.G. was supported by a Marie-Curie International Outgoing Fellowship from the European Union (PIOF-2013-624924).

Althepus pictus Thorell, 1898 is the type species of the genus Althepus Thorell, 1898 from the family Psilodercidae Machado, 1951. This genus includes 60 species from Southeast Asia (WSC 2020). A. pictus was described on the basis of one male and one female from Carin Chebà mountains, elevation 600‒800 m, Kayin Province, Myanmar. Another female specimen lacking several legs was found in Farm Caves in Mawlamyine, Mon State, Myanmar. The original description was in Latin and without any figures. Fage (1912) redescribed it based on the same male and female type specimens from Carin Chebà, but without mentioning the female from Farm Caves. Fage (1912) provided measurements, but the figures of the male right palp are imprecise. The species is redescribed here based on the original male and female type specimens deposited in Museo Civico di Storia Naturale ‘Giacomo Doria’ (MSNG) in Italy. The male and female type specimens are the only known material of A. pictus. No information is available on the female specimen from Farm Caves, which maybe have been lost. No fresh material of this species has been collected in region during five subsequent expeditions to Myanmar tours organized by the Southeast Asia Biodiversity Research Institute in the years 2016–2020.

A new genus and three new species of the spider family Palpimanidae Thorell, 1870 from Kenya are described. Sceliscelis Oketch & Li, gen. nov. is close to Sarascelis Simon, 1887 and Scelidocteus Simon, 1907 but differs in the structure of the male palp. The new species reported are Sceliscelis marshi Oketch & Li, sp. nov., Scelidocteus taitave Oketch & Li, sp. nov., and Hybosida machondogo Oketch & Li, sp. nov.Sceliscelis marshisp. nov. is described from males and females collected from Tsavo in south Kenya. Scelidocteus taitavesp. nov. can be distinguished from other congeners, as well as from the morphologically similar Scelidomachus socotranus Pocock, 1899, by the shape of the palpal “conductor”. Hybosida machondogosp. nov. differs from other six-eyed Hybosida spp. by possessing rudimentary posterior median eyes.

The genus Pholcus Walckenaer, 1805 is reported from Pakistan for the first time. Two new species of the Pholcus nenjukovi species-group are described: Pholcus hamuchal Yao & Li sp. nov. (Gilgit Baltistan, male and female) and Pholcus kalam Yao & Li sp. nov. (Khyber Pakhtunkhwa, male and female). Type material is deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS) in Beijing, China.

Background Bladder cancer (BC) is the most common malignancy of urinary system and cisplatin (DDP) remains the only chemotherapy option for treatment of BC at the advanced stage. The critical molecules involved in the regulation of cisplatin resistance are still largely unknown. CircRNAs has been demonstrated to be involved in tumorigenesis and development and drug resistance of various cancer cells. CircCEP128 contributed to BC progression by regulating miR-145-5p/MYD88/MAKP axis. However, functions and molecular mechanisms of circCEP128 in DDP resistance of bladder cancer cells still remain largely unclear. Methods Bladder cancer tissue and the corresponding adjacent normal tissue as well as serum samples were obtained from a total of 60 BC patients who received the same cisplatin-based chemotherapy. The expression level of circCEP128 in tissues and serums was measured using qRT-PCR. WB was utilized to detect expression level of PCNA, Cyclin D1, RIPK3, p-RIPK3, MLKL or p-MLKL. Functionally, BC cell viability and proliferation are measured through relevant experiments, including CCK8 assay and cell colony formation assay. Results In the current study, we demonstrated that circCEP128 expression was distinctly elevated in the BC tissues and serums, especially in the chemoresistant BC tissues or cell lines, correlated with poor prognosis of BC patients. In addition, ROC curve suggested that circCEP128 might serve as an effective diagnostic biomarker for BC and treatment. Furthermore, cell function assays showed that circCEP128 silencing by siRNA could reverse the drug-resistance of BC cells to cisplatin by inducing necroptosis through regulation of RIPK3/MLKL signaling pathway. Conclusions Our findings indicated that circCEP128 may serve as a valuable diagnostic biomarker in BC and contribute to cisplatin resistance of bladder cancer cells by repressing necroptosis through RIPK3/MLKL signaling pathway. These findings provide novel insights into the role of circCEP128 as a biomarker for the diagnosis and treatment target of BC.

Immune therapies have transformed the cancer therapeutic landscape but fail to benefit most patients. To elucidate the underlying mechanisms by which T cells mediate elimination of leukemia, we generated a high-resolution map of longitudinal T cell dynamics within the same tumor microenvironment (TME) during response or resistance to donor lymphocyte infusion (DLI), a widely used immunotherapy for relapsed leukemia. We analyzed 87,939 bone marrow-derived single T cell transcriptomes, along with chromatin accessibility and single T cell receptor clonality profiles, by developing novel machine learning tools for integrating longitudinal and multimodal data. We found that pre-treatment enrichment and post-treatment rapid, durable expansion of ‘terminal’ (TEX) and ‘precursor’ (TPEX) exhausted subsets, respectively, defined DLI response. A contrasting, heterogeneous pattern of T cell dysfunction marked DLI resistance. Unexpectedly, TPEX cells that expanded in responders did not arise from the infusion product but instead from both pre-existing and novel clonotypes recruited to the TME. Our unbiased dissection of the TME using a Bayesian method, Symphony, defined the T cell circuitry underlying effective human anti-leukemic immune responses that may be broadly relevant to other exhaustion antagonists across cancers. Finally, we provide a general analysis paradigm for exploiting temporal single-cell genomic profiling for deep understanding of therapeutic scenarios beyond oncology.

The genus Belisana Thorell, 1898 is diverse in southern China. In this study, six new species are described and illustrated: Belisana guilin sp. nov. (Guangxi; male, female), Belisana maoer sp. nov. (Sichuan; male, female), Belisana naling sp. nov. (Guangxi; male, female), Belisana xiyuan sp. nov. (Fujian; male, female), Belisana xuanguan sp. nov. (Guangxi; male) and Belisana yuexiu sp. nov. (Guangdong; male). In addition, Belisana is reported from Sichuan for the first time.

Crassignatha Wunderlich, 1995 is redefined to include species with six eyes in three diads, chelicerae fused only near the base, sculpturing on the carapace, one or two clasping spurs on tibia II, a bilateral scutum of the male abdomen, and globular spermathecae and adjacent copulatory openings in the female. A key and distribution map are provided for 24 Crassignatha species in this paper. Diagnoses and illustrated photographs are provided for 22 species from China, Malaysia, Thailand, and Vietnam. Thirteen species are described and documented as new to science: C. baihua Y. Lin & S. Li, sp. nov. (♂♀), C. bangbie Y. Lin & S. Li, sp. nov. (♀), C. changyan Y. Lin & S. Li, sp. nov. (♀), C. dongnai Y. Lin & S. Li, sp. nov. (♀), C. gucheng Y. Lin & S. Li, sp. nov. (♂♀), C. mengla Y. Lin & S. Li, sp. nov. (♂♀), C. nantou Y. Lin & S. Li, sp. nov. (♂♀), C. nasalis Y. Lin & S. Li, sp. nov. (♂♀), C. rostriformis Y. Lin & S. Li, sp. nov. (♂♀), C. shunani Y. Lin & S. Li, sp. nov. (♂♀), C. si Y. Lin & S. Li, sp. nov. (♂♀), C. thamphra Y. Lin & S. Li, sp. nov. (♀), and C. xichou Y. Lin & S. Li, sp. nov. (♀). Three new combinations are proposed: C. bicorniventris (Lin & Li, 2009), comb. nov., C. quadriventris (Lin & Li, 2009), comb. nov., and C. shiluensis (Lin & Li, 2009), comb. nov. are transferred from Patu Marples, 1951. DNA barcodes and genetic distances of seventeen species are obtained to confirm correct identification. Types of seven known Chinese Crassignatha species are re-examined, and the taxonomic placement of C. longtou Miller, Griswold & Yin, 2009 may be incorrect based on morphological and molecular data.

Only three species of the genus Belisana Thorell, 1898, were recorded from Tibet, China, before the current study. In this study, four new Belisana species from Tibet are described: Belisana medog sp. nov. (male), Belisana muruo sp. nov. (male, female), Belisana xigaze sp. nov. (male, female), and Belisana zham sp. nov. (male, female). The female of Belisana gyirong Zhang, Zhu & Song, 2006 is reported for the first time.

Four new species of the genusCheiracanthiumC.L. Koch, 1839 from Xishuangbanna, Yunnan Province, China are described:C. daofengYu & Li,sp. nov.(♂♀),C. duanbiYu & Li,sp. nov.(♂♀),C. gouYu & Li,sp. nov.(♂), andC. wuquanYu & Li,sp. nov.(♀). In addition,SinocanthiumYu & Li,gen. nov., is described with the type speciesS. shuangqiuYu & Li,sp. nov.A key to cheiracanthiid genera distributed in East and Southeast Asia is provided.

The genus Savarna Huber, 2005 comprises only five species, from southern Thailand, Peninsular Malaysia and Sumatra. In this study, five new species are described from Thailand: Savarna bannang sp. nov. (Yala), S. chiangmai sp. nov. (Chiangmai), S. huahin sp. nov. (Prachuap Kiri Khan), S. satun sp. nov. (Satun), S. thungsong sp. nov. (Nakhon Srithammarat). All new species are described from males and females. The distribution of S. chiangmai sp. nov. represent the northernmost record of the genus.

VIVANT; Hotspot mutation of IKZF3 (IKZF3-L162R) has been identified as a putative driver of chronic lymphocytic leukemia (CLL), but its function remains unknown. Here, we demonstrate its driving role in CLL through a B cell-restricted conditional knockin mouse model. Mutant Ikzf3 alters DNA binding specificity and target selection, leading to hyperactivation of B cell receptor (BCR) signaling, overexpression of nuclear factor κB (NF-κB) target genes, and development of CLL-like disease in elderly mice with a penetrance of ~40%. Human CLL carrying either IKZF3 mutation or high IKZF3 expression was associated with overexpression of BCR/NF-κB pathway members and reduced sensitivity to BCR signaling inhibition by ibrutinib. Our results thus highlight IKZF3 oncogenic function in CLL via transcriptional dysregulation and demonstrate that this pro-survival function can be achieved by either somatic mutation or overexpression of this CLL driver. This emphasizes the need for combinatorial approaches to overcome IKZF3-mediated BCR inhibitor resistance.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Lung regeneration occurs in a variety of adult mammals after surgical removal of one lung (pneumonectomy). Previous studies of murine post-pneumonectomy lung growth have identified regenerative “hotspots” in subpleural alveolar ducts; however, the cell-types participating in this process remain unclear. To identify the single cells participating in post-pneumonectomy lung growth, we used laser microdissection, enzymatic digestion and microfluidic isolation. Single-cell transcriptional analysis of the murine alveolar duct cells was performed using the C1 integrated fluidic circuit (Fluidigm) and a custom PCR panel designed for lung growth and repair genes. The multi-dimensional data set was analyzed using visualization software based on the tSNE algorithm. The analysis identified 6 cell clusters; 1 cell cluster was present only after pneumonectomy. This post-pneumonectomy cluster was significantly less transcriptionally active than 3 other clusters and may represent a transitional cell population. A provisional cluster identity for 4 of the 6 cell clusters was obtained by embedding bulk transcriptional data into the tSNE analysis. The transcriptional pattern of the 6 clusters was further analyzed for genes associated with lung repair, matrix production, and angiogenesis. The data demonstrated that multiple cell-types (clusters) transcribed genes linked to these basic functions. We conclude that the coordinated gene expression across multiple cell clusters is likely a response to a shared regenerative microenvironment within the subpleural alveolar ducts.

Background: Chlorine gas (Cl2) exposure remains a public health concern in household, occupational, and transportation accidents around the world. The death rate associated with acute respiratory distress syndrome (ARDS) caused by high concentrations of Cl2 is very high, mainly because the pathogenesis of ARDS is still not very clear. Histone H4 has been identified as an important endogenous pro-inflammatory molecule. The present work aimed to study the pathogenic role of histone H4 in Cl2 induced ARDS. Methods: ARDS was induced by Cl2 exposure in male C57BL/6 mice. Circulating histone H4, blood gas, pulmonary edema, endothelial activation, and neutrophil infiltration were measured during acute lung injury. Histone H4 or anti-H4 antibody was administered through tail vein 1h prior to Cl2 exposure to study the pathogenic role of histone H4. The Toll-like receptor 2 knock-out (Tlr2-KO), Tlr4-KO mice and the blocking antibody against TLR1, TLR2, TLR4 or TLR6 were used to explore the mechanism involved in histone H4 mediated injury. Results: Cl2 exposure induced a concentration dependent acute lung injury. The levels of circulating histone H4 were positively correlated with the concentrations of Cl2. Pretreatment with intravenous histone H4 further aggravated lethality rate, blood gas, endothelial activation, and neutrophil infiltration while the anti-H4 antibody showed protective effects. The deficiency of Tlr4 improved lethality rate, blood gas, and pulmonary edema; prevented endothelial and neutrophil activation caused by Cl2 exposure. More importantly, the gene deletion of Tlr4 diminished greatly the effect of histone H4 or anti-H4 antibody observed in the wild-type (WT) mice. The impact of Tlr2 on inflammatory injury was not significant. The role of TLRs was also validated by endothelial activation mediated by histone H4 in vitro. Conclusions: Circulating histone H4 played a pro-inflammatory role in ARDS caused by Cl2. TLR4 was closely involved in histone H4 mediated inflammatory injury. The intervention targeted at histone H4 is potentially protective.

Two new species of the spider genus Wanniyala Huber & Benjamin, 2005 are described from Sri Lanka: W. badulla sp. nov. (Uva Province; male and female) and W. batatota sp. nov. (Sabaragamuwa Province; male and female). In addition, new records of W. mudita Huber, 2019 (Western Province; male) and W. viharekele Huber, 2019 (Southern Province; male and female) are provided.

The genus Pholcus Walckenaer, 1805 is composed of 21 species-groups and the P. yichengicus species-group contains 35 species from central and southern China, and Thailand. In this study, two new species of the P. yichengicus species-group are described from southern China: Pholcus jingnan Yao & Li sp. nov. (Guizhou, male and female) and Pholcus longlin Yao & Li sp. nov. (Guangxi, male and female).

The spider genus Desis Walckenaer, 1837 is the type genus of the spider family Desidae Pocock, 1895. Desis spiders hide in silk sacs between rocks or shells during high tide and forage during low tide (Baehr et al. 2017). Four Desis species have been recorded from Asia: Desis gardineri Pocock, 1904 (India), Desis inermis Gravely, 1927 (India), Desis japonica Yaginuma, 1956 (Japan) and Desis martensi L. Koch, 1872 (Malaysia) (World Spider Catalog 2020). Until now, only one species of the family Desidae, Badumna tangae Zhu, Zhang & Yang, 2006, has been reported from China (Zhu et al. 2006). Here, we describe a new species of Desis and report the genus from China for the first time.

Two new genera and eight new species of jumping spiders from Xishuangbanna Tropical Botanical Garden (XTBG) are diagnosed, described, and illustrated. The new genera are Dendroiciusgen. nov. (type species D. hotaruaesp. nov. (♂♀)) and Megaeupoagen. nov. (type species M. yanfengisp. nov. (♂♀)). The new species are Colyttus yiwuisp. nov. (♂♀), Euophrys xuyeisp. nov. (♂♀), Foliabitus weihangisp. nov. (♂♀), Nigorella menglasp. nov. (♂♀), Onomastus chenaesp. nov. (♂♀), and Synagelides platnickisp. nov. (♂♀). A new combination is proposed: Megaeupoa gravelyi (Caleb, 2018), comb. nov., ex Brettus Thorell, 1895. Two new synonyms have been proposed: Irura prima (Żabka, 1985), syn. nov. with Irura mandarina Simon, 1903; Evarcha digitata Peng & Li, 2002, syn. nov. with Ptocasius montiformis Song, 1991.

Three new species of the spider genus Belisana Thorell, 1898 are described based on material collected in Xishuangbanna, Yunnan, China: Belisana mengla Yao & Li sp. nov. (male, female), Belisana menglun Yao & Li sp. nov. (male), and Belisana mengyang Yao & Li sp. nov. (male, female), bringing the total Belisana fauna of Xishuangbanna to 12 species.

A new genus of the spider family Deinopidae C.L. Koch, 1850 is described from Asia: Asianopis Lin & Li gen. nov., with A. zhuanghaoyuni Lin & Li sp. nov. as the type species. The new genus is divided into two species groups, of which the liukuensis-group includes two species: A. dumogae (Merian, 1911) sp. reval. comb. nov. (♀) and A. liukuensis (Yin, Griswold & Yan, 2002) comb. nov. (♂♀); and the zhuanghaoyuni-group comprises five species: A. celebensis (Merian, 1911) comb. nov. (♂), A. konplong (Logunov, 2018) comb. nov. (♂), A. wangi Lin & Li sp. nov. (♂♀), A. wuchaoi Lin & Li sp. nov. (♂♀), and A. zhuanghaoyuni Lin & Li sp. nov. All previously described species are transferred from Deinopis MacLeay, 1839. Deinopis scrubjunglei Caleb & Mathai, 2014 is treated as a junior synonym of Asianopis liukuensiscomb. nov.

Eight new species of the spider genus Pimoa Chamberlin & Ivie, 1943 are described from Tibet, China: P. cona Zhang & Li, sp. nov. (♂♀), P. duiba Zhang & Li, sp. nov. (♂♀), P. lemenba Zhang & Li, sp. nov. (♀), P. mainling Zhang & Li, sp. nov. (♂♀), P. nyingchi Zhang & Li, sp. nov. (♂♀), P. rongxar Zhang & Li, sp. nov. (♂♀), P. samyai Zhang & Li, sp. nov. (♂♀), and P. yadong Zhang & Li, sp. nov. (♂♀). The DNA barcodes of the eight new species are documented.

Figure S1. Single cell DNA-seq of singly-edited Ba/F3 cell lines. QC metrics of single-cell DNA-seq analysis by Tapestri including number of sequencing reads and targeted amplicon coverage, analysis of percent modified reads across on and off-targets and zygosity analysis of on-targets. Figure S2. Single cell qPCR-based detection of sgRNAs. Analysis of number and co-occurrence of sgRNAs in single Ba/F3 cells, as assessed via qPCR-based detection. (DOCX 689 kb)

Seven new species of jumping spiders collected from Xishuangbanna Tropical Botanical Garden in Yunnan, China, are diagnosed and described: Charippus yinae sp. nov. (♂♀), Chinattus inflatus sp. nov. (♂), Indomarengo yui sp. nov. (♂), Phintella banna sp. nov. (♂♀), P. mii sp. nov. (♂♀), Simaetha menglun sp. nov. (♂♀) and S. pengi sp. nov. (♂♀). Charippus yinae sp. nov. is the second species of the genus Charippus Thorell, 1895, which was previously known only from one sex.

Eight new species of the spider genus Pimoa Chamberlin & Ivie, 1943 are described from Tibet, China: P. cona Zhang & Li, sp. nov. (♂♀), P. duiba Zhang & Li, sp. nov. (♂♀), P. lemenba Zhang & Li, sp. nov. (♀), P. mainling Zhang & Li, sp. nov. (♂♀), P. nyingchi Zhang & Li, sp. nov. (♂♀), P. rongxar Zhang & Li, sp. nov. (♂♀), P. samyai Zhang & Li, sp. nov. (♂♀), and P. yadong Zhang & Li, sp. nov. (♂♀). The DNA barcodes of the eight new species are documented.

The genus Psiloderces Simon, 1892 is the second largest genus of Psilodercidae, a family restricted to Asia, occurring from East India to the Philippines. Fourteen new species of Psiloderces from Indonesia, the Philippines, and Vietnam are described: P. heisesp. nov. (♂♀), P. gawanaensissp. nov. (♂♀), P. bontocensissp. nov. (♀), P. cuyapoensissp. nov. (♂♀), P. xichangsp. nov. (♂♀), P. cattienensissp. nov. (♂♀), P. pingguosp. nov. (♂♀), P. palopoensissp. nov. (♂♀), P. penajamensissp. nov. (♂), P. grohotensissp. nov. (♂♀), P. bangkiraiensissp. nov. (♂♀), P. bolangsp. nov. (♂♀), P. wangousp. nov. (♂♀), and P. malinoensissp. nov. (♂♀). Types are deposited in the Institute of Zoology, Chinese Academy of Sciences (IZCAS) in Beijing.

Previously, the genus Merizocera Fage, 1912 comprised only seven species from Indonesia, Malaysia, Sri Lanka, and Thailand. In this study, 28 new species are described from South and Southeast Asia: M. baoshan Li, sp. nov. (♂♀), M. betong Li, sp. nov. (♂♀), M. colombo Li, sp. nov. (♂♀), M. galle Li, sp. nov. (♂♀), M. hponkanrazi Li, sp. nov. (♂), M. kachin Li, sp. nov. (♂♀), M. kandy Li, sp. nov. (♂♀), M. mandai Li, sp. nov. (♂♀), M. krabi Li, sp. nov. (♂♀), M. kurunegala Li, sp. nov. (♂♀), M. lincang Li, sp. nov. (♀), M. mainling Li, sp. nov. (♂♀), M. nyingchi Li, sp. nov. (♀), M. peraderiya Li, sp. nov. (♂♀), M. phuket Li, sp. nov. (♂♀), M. putao Li, sp. nov. (♂♀), M. ranong Li, sp. nov. (♂♀), M. ratnapura Li, sp. nov. (♂♀), M. salawa Li, sp. nov. (♂), M. tak Li, sp. nov. (♀), M. tanintharyi Li, sp. nov. (♂♀), M. tengchong Li, sp. nov. (♂), M. thenna Li, sp. nov. (♂♀), M. uva Li, sp. nov. (♀), M. wenshan Li, sp. nov. (♂♀), M. wui Li, sp. nov. (♂♀), M. yala Li, sp. nov. (♀), and M. yuxi Li, sp. nov. (♂♀). Among them the genus Merizocera is reported for the first time from China, Myanmar, and Singapore.

Species of the spider family Hypochilidae Marx, 1888 from China are studied, including two known species and two new species of the genus Ectatosticta Simon, 1892. The new species are E. wukongsp. nov. (♂♀) from Sichuan and E. xuanzangsp. nov. (♀) from Tibet.

Six species of the genus Trilacuna Tong & Li, 2007 are reported from Myanmar, including four new species: T. besucheti Grismado & Piacentini, 2014 (♂♀), T. changzi Tong & Li, sp. nov. (♂♀), T. hponkanrazi Tong & Li, sp. nov. (♂♀), T. loebli Grismado & Piacentini, 2014 (♀), T. triseta Tong & Li, sp. nov. (♂), and T. zhigangi Tong & Li, sp. nov. (♀). Morphological descriptions and photographic illustrations of the new species are given. All types are preserved in the Institute of Zoology, Chinese Academy of Sciences in Beijing (IZCAS).

BACKGROUND The study was aimed to investigate the influence of circ_0058063 on tumorigenesis as well as the regulatory mechanism of circ_0058063/miR-145-5p/ CDK6 pathway in bladder cancer (BC). METHODS Bioinformatics analysis was used to screen highly expressed circle RNA (circRNA) and search its downstream microRNA (miRNA) and protein. The expression level of circRNA, miRNA, and CDK6 in BC cell lines T24 and J82 were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. Small interfering RNA was used to downregulate circ_0058063 expression. Cell proliferation, cell cycle, cell apoptosis, and cell migration of T24 cells and J82 cells were detected through MTT assay, flow cytometry, and wound-healing assay, respectively. The relationships among miR-145-5p, circ_0058063, and CDK6 were confirmed through dual luciferase reporter assay. In vivo experiment was also performed to explore the impact of circ_0058063/miR-145-5p/ CDK6 pathway on tumorigenesis in BALB/c nude mice. RESULTS Circ_0058063 was significantly overexpressed in BC tissues. The downregulation of circ_0058063 impaired BC cell proliferation and migration ability but improved cell apoptosis ability. Circ_0058063 repressed miR-145-5p, which inhibited the expression of CDK6. Downregulation of circ_0058063 or miR-145-5p transfection contributed to more cells arresting in G0/G1 stage. MiR-145-5p suppressed cell growth and migration ability in BC, whereas CDK6 exerted the opposite influence on these cellular events. In vivo experiment also indicated that tumor development in BALB/c nude mice was repressed remarkably when circ_0058063 was downregulated. CONCLUSION Circ_0058063 acted as a sponge of miR-145-5p to promote BC progression by regulating CDK6 expression, which provided some potential targets for BC treatment.

Sixteen new species ofPseudopodaJäger, 2000 (Sparassidae, Heteropodinae) are described. Among them, eight species were collected from China:P.chayuensisZhao & Li,sp. n.(♂),P.conaensisZhao & Li,sp. n.(♂),P.medogensisZhao & Li,sp. n.(♂),P.nyingchiensisZhao & Li,sp. n.(♂),P.shacunensisZhao & Li,sp. n.(♂),P.shuoZhao & Li,sp. n.(♂♀),P.yuanjiangensisZhao & Li,sp. n.(♀) andP.zixiensisZhao & Li,sp. n.(♂); seven from Myanmar:P.colubrinaZhao & Li,sp. n.(♂♀),P.daxingZhao & Li,sp. n.(♂),P.gexiaoZhao & Li,sp. n.(♂),P.putaoensisZhao & Li,sp. n. (♂),P.subbirmanicaZhao & Li,sp. n.(♂♀),P.titanZhao & Li,sp. n.(♂♀),P.xiaZhao & Li,sp. n.(♂); and one from Thailand:P.maeklongensisZhao & Li,sp. n.(♂). A distribution map of the new species is also provided.

A new species of subterranean amphipod,BogidiellapingxiangensisHou & Li,sp. n., is described from Xiongshizilong Cave in Pingxiang City, China. The new species is characterized by having the bases of pereopods III and V expanded; the inner ramus of pleopods I–III with one segment; the telson longer than wide and with the apical margin with a shallow U-shaped excavation. DNA barcode of the new species is documented as support of molecular differences between related species.

ThePinelemabailongensisWang & Li, 2012 species group of the spider family Telemidae Fage, 1913 from Guangxi and Guizhou, China is revised. Previously, this species group contained two species:P.bailongensisandP.xiushuiensisWang & Li, 2016. In this study, four species are transferred fromTelemaSimon, 1882 toPinelemaWang & Li, 2012, and treated as members of theP.bailongensisspecies group. They areP.cordata(Wang & Li, 2010)comb. n.,P.liangxi(Zhu & Chen, 2002)comb. n.,P.strentarsi(Lin & Li, 2010)comb. n.andP.zhewang(Chen & Zhu, 2009)comb. n.Additionally, six new species belonging to the species group are described:P.cheniZhao & Li,sp. n.(♂♀),P.huoyanZhao & Li,sp. n.(♂♀),P.lizhuangZhao & Li,sp. n.(♂♀),P.wangshangZhao & Li,sp. n.(♂♀),P.wenyangZhao & Li,sp. n.(♂♀) andP.yunchuniZhao & Li,sp. n.(♂♀). A key to males is provided.

A new genus of the subfamily Coelotinae F.O. Pickard-Cambridge, 1893, Vappolotes Zhao et S. Li gen. n., with two new species, V. ganlongensis Zhao et S. Li sp. n. (♂♀) and V. jianpingensis Zhao et S. Li sp. n. (♀), is described. The genus is restricted to southern China (Guizhou). Its relationship to other coelotine genera is discussed. A partial fragment of the mitochondrial cytochrome oxidase subunit I of both species were obtained to aid species identification at the molecular level.

Expression quantitative trait loci (eQTL) studies illuminate the genetics of gene expression and, in disease research, can be particularly illuminating when using the tissues directly impacted by the condition. In nephrology, there is a paucity of eQTL studies of human kidney. Here, we used whole-genome sequencing (WGS) and microdissected glomerular (GLOM) and tubulointerstitial (TI) transcriptomes from 187 individuals with nephrotic syndrome (NS) to describe the eQTL landscape in these functionally distinct kidney structures. Using MatrixEQTL, we performed cis-eQTL analysis on GLOM (n = 136) and TI (n = 166). We used the Bayesian “Deterministic Approximation of Posteriors” (DAP) to fine-map these signals, eQTLBMA to discover GLOM- or TI-specific eQTLs, and single-cell RNA-seq data of control kidney tissue to identify the cell type specificity of significant eQTLs. We integrated eQTL data with an IgA Nephropathy (IgAN) GWAS to perform a transcriptome-wide association study (TWAS). We discovered 894 GLOM eQTLs and 1,767 TI eQTLs at FDR < 0.05. 14% and 19% of GLOM and TI eQTLs, respectively, had >1 independent signal associated with its expression. 12% and 26% of eQTLs were GLOM specific and TI specific, respectively. GLOM eQTLs were most significantly enriched in podocyte transcripts and TI eQTLs in proximal tubules. The IgAN TWAS identified significant GLOM and TI genes, primarily at the HLA region. In this study, we discovered GLOM and TI eQTLs, identified those that were tissue specific, deconvoluted them into cell-specific signals, and used them to characterize known GWAS alleles. These data are available for browsing and download via our eQTL browser, “nephQTL.”

A new genus of the subfamily Coelotinae F.O. Pickard-Cambridge, 1893, Sinodraconarius gen. n., with four new species, S.cawarongensis sp. n. (♂♀), S.muruoensis sp. n. (♂♀), S.sangjiuensis sp. n. (♂♀, type species), S.yui sp. n. (♂♀) and S.patellabifidus (Wang, 2003) comb. n., ex. Draconarius Ovtchinnikov, 1999 is described. The genus is restricted to Southwest China. Sinodraconarius gen. n. is most similar to Draconarius but can be distinguished by the shape of the copulatory organs. The DNA barcodes of all species were documented for future use.

Seven new species of the genusGammarusare described and illustrated from southern China. The new speciesGammarusvalleculaHou & Li,sp. n.,G.qinlingHou & Li,sp. n.,G.zhigangiHou & Li,sp. n.andG.jidutanxianHou & Li,sp. n.are characterized by inner ramus of uropod III half the length of outer ramus.GammaruslongdongHou & Li,sp. n.is characterized by inner ramus of uropod III 0.9 times as long as outer ramus.GammarusmosuoHou & Li,sp. n.is characterized by pereopods V–VII with long setae on anterior margins and both rami of uropod III armed with simple setae.GammaruscaecigenusHou & Li,sp. n.can be distinguished from other species by eyes absent. DNA barcodes of the new species are documented as proof of molecular differences between species. A key to the new species and a map of their distributions are provided.

We investigated thoroughly the effect of lncRNA PART1 on prostate cancer cells proliferation and apoptosis, through regulating toll-like receptor (TLR) pathways. LncRNA PART1 expression was also examined by quantitative real-time polymerase chain reactions (qRT-PCR) in human tissues and the cells lines LNCaP and PC3. After transfection with si-PART1 or control constructs, the cell viability was measured by MTS and colony formation assays. In addition, the apoptosis rate of the prostate cancer cells was validated by TUNEL staining. Relationships between lncRNA PART1 expression and TLR pathway genes were demonstrated by qRT-PCR and Western blotting. High levels of lncRNA PART1 expression were correlated with advanced cancer stage and predication of poor survival. LncRNA PART1 levels was increased in PCa cells treated with 5α-dihydrotestosterone (DHT), confirming PART1 was directly induced by androgen. Moreover, down-regulation of lncRNA PART1 inhibited prostate cancer cell proliferation and accelerated cell apoptosis. In addition, lncRNA PART1 induced downstream genes expression in TLR pathways includingTLR3,TNFSF10andCXCL13to further influence prostate cancer cells, indicating its carcinogenesis on prostate cancer. LncRNA PART1 promoted cell proliferation ability and apoptosis via the inhibition of TLR pathways in prostate cancer. LncRNA PART1 could hence be considered as a new target in the treatment of prostate cancer.

Four new species of the genusGammarusare described and illustrated from Tibetan Plateau.Gammarusaltussp. n.andG.limosussp. n.are characterized by pereopods III–IV with a few short setae and uropod III with marginal spines accompanied by short setae.Gammaruskangdingensissp. n.andG.gonggaensissp. n.are characterized by pereopods III–IV with long straight setae on posterior margins and inner ramus of uropod III 0.4 times as long as outer ramus. Detailed morphological comparisons with related species are discussed. A key to 15Gammarusspecies from the Tibetan Plateau and a map of their distributions are provided.